Many genetic disorders, including cancer, can result from the translocation of genes to novel chromatin environments that influence the fidelity of their expression. Position effect variegation (PEV) is a well documented and described phenomenon that results from the repression of genes that have been inserted within or juxtaposed near heterochromatin, following a chromosomal translocation or inversion. The research proposed here should elucidate a more clear understanding of the protein machinery involved in the formation of gene repressive heterochromatin, their influence on PEV and the manner in which individual protein constituents interact with one another within heterochromatin. Furthermore, I will test the possibility that gene repressive heterochromatin can be established selectively in the genome, providing the skeletal framework for gene therapy in patients suffering from genetic disorders where the expression of a mutated or translocated gene is detrimental.